trans-ISRIB (#75845) Datasheet Without Images Cell Signaling Technology

For Research Use Only. Not for Use in Diagnostic Procedures.

Background

Trans-integrated stress response inhibitor (trans-ISRIB) is a small-molecule inhibitor of the cellular integrated stress response (ISR). The ISR is a coordinated collection of signaling pathways that activate different eukaryotic initiation factor 2 (eIF2) kinases to phosphorylate the subunit eIF2α. trans-ISRIB strongly (IC₅₀ = 5 nM) reverses the effects of eIF2α phosphorylation in cells undergoing ISR (1). Phosphorylation of eIF2α stabilizes and inhibits turnover of the eIF2β protein complex (2). Both trans-ISRIB and eIF2(αP) bind to distinct sites within the guanine nucleotide exchange factor eIF2β. trans-ISRIB inhibits the ISR by promoting eIF2β nucleotide exchange activity and antagonizing the inhibitory effect of eIF2(αP) on eIF2β activity. Simultaneous binding of eIF2(αP) to eIF2β regulatory sites deforms the trans-ISRIB-binding pocket and prevents trans-ISRIB inhibition of the ISR (3). Because heightened ISR is sometimes associated with unfavorable outcomes, trans-ISRIB treatment can provide beneficial effects in models of neurodegeneration, chronic demyelination, and head injury (4-6).

Molecular Formula

C₂₂H₂₄Cl₂N₂O₄

Molecular Weight

451.3 g/mol

Purity

>98%

CAS

1597403-47-8

Solubility

Soluble in DMSO at 5 mg/mL.

Storage

Store lyophilized at -20ºC, desiccated. In lyophilized form, the chemical is stable for 24 months. Once in solution, store at -20ºC and use within 3 months to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Directions for Use

trans-ISRIB is supplied as a lyophilized powder. For a 10 mM stock, reconstitute 5 mg of powder in 1.11 mL of DMSO. Working concentrations and length of treatment can vary depending on the desired effect.

Background References

Cross-Reactivity Key

H: human M: mouse R: rat Hm: hamster Mk: monkey Vir: virus Mi: mink C: chicken Dm: D. melanogaster X: Xenopus Z: zebrafish B: bovine Dg: dog Pg: pig Sc: S. cerevisiae Ce: C. elegans Hr: horse GP: Guinea Pig Rab: rabbit All: all species expected

Trademarks and Patents

Cell Signaling Technology is a trademark of Cell Signaling Technology, Inc.

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